Advertisement |  | | Genomic know-how® - it's how experiments succeed. You need answers to complex biological questions. We have deep expertise across a wide range of technologies to help you get it right the first time. At EA | Quintiles, our experienced scientists leverage innovative bioinformatics and methodologies to give you the genomic information you need to succeed. genomicknowhow.com |  | | | |  | TABLE OF CONTENTS
| May 2014 Volume 46, Issue 5 |  | | |  |  Editorial
News and Views
Research Highlights
Brief Communications
Article
Letters
| | | | | |
Advertisement | | The Leena Peltonen School of Human Genomics (17-21 August 2014)
Wellcome Trust Genome Campus, Hinxton, UK
Final applications are invited for this Wellcome Trust Summer School, which provides an opportunity for PhD students to learn from and be inspired by those that have shaped our understanding of human genomics in the past decade. Application Deadline: 15 May 2014 |  | | | | | | | Advertisement | | 
Nature Genetics, Chinese Academy of Medical Sciences and Anhui Medical University are pleased to present:
Genome Variation in Precision Medicine
May 15-17, 2014 Radegast Lake View Hotel Beijing
Click here for more information or to register for this conference today | | | | | | | Editorial |  Top | |  | | Researching the researchers p417
doi:10.1038/ng.2972
Francis Collins, director of the US National Institutes of Health, recently highlighted in Nature the need to identify and correct systematic problems in biomedical research. One such effort, the Stanford Meta-Research Innovation Center, will monitor the practice of research and suggest policies for improvement. We commend this initiative that supports our commitment to publishing scientifically rigorous research.
| | News and Views | Top | | | | | | Research Highlights | Top | | | | Clinical genome interpretation | Oncogenic chimeric transcript | Epigenetic reprogramming in treatment-resistant breast cancer | MRSA toxicity and virulence | Organizing the body axis | Brief Communications | Top | | | | Recurrent SMARCA4 mutations in small cell carcinoma of the ovary pp424 - 426
Petar Jelinic, Jennifer J Mueller, Narciso Olvera, Fanny Dao, Sasinya N Scott, Ronak Shah, JianJiong Gao, Nikolaus Schultz, Mithat Gonen, Robert A Soslow, Michael F Berger & Douglas A Levine
doi:10.1038/ng.2922
Douglas Levine and colleagues identify recurrent inactivating mutations in the SWI/SNF complex member SMARCA4 in 12 of 12 samples of small cell carcinoma of the ovary, hypercalcemic type. These findings open the door for the development of targeted therapies to treat this rare but deadly cancer.
| | | | Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4 pp427 - 429
Pilar Ramos, Anthony N Karnezis, David W Craig, Aleksandar Sekulic, Megan L Russell, William P D Hendricks, Jason J Corneveaux, Michael T Barrett, Karey Shumansky, Yidong Yang, Sohrab P Shah, Leah M Prentice, Marco A Marra, Jeffrey Kiefer, Victoria L Zismann, Troy A McEachron, Bodour Salhia, Jaime Prat, Emanuela D'Angelo, Blaise A Clarke, Joseph G Pressey, John H Farley, Stephen P Anthony, Richard B S Roden, Heather E Cunliffe, David G Huntsman & Jeffrey M Trent
doi:10.1038/ng.2928
Jeffrey Trent, David Huntsman and colleagues identify the SWI/SNF chromatin-remodeling gene SMARCA4 as commonly mutated in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Their results implicate SMARCA4 as a crucial factor in the oncogenesis of SCCOHT, a rare but highly malignant cancer.
| | Article | Top | | | | Heritability and genomics of gene expression in peripheral blood pp430 - 437
Fred A Wright, Patrick F Sullivan, Andrew I Brooks, Fei Zou, Wei Sun, Kai Xia, Vered Madar, Rick Jansen, Wonil Chung, Yi-Hui Zhou, Abdel Abdellaoui, Sandra Batista, Casey Butler, Guanhua Chen, Ting-Huei Chen, David D'Ambrosio, Paul Gallins, Min Jin Ha, Jouke Jan Hottenga, Shunping Huang, Mathijs Kattenberg, Jaspreet Kochar, Christel M Middeldorp, Ani Qu, Andrey Shabalin, Jay Tischfield, Laura Todd, Jung-Ying Tzeng, Gerard van Grootheest, Jacqueline M Vink, Qi Wang, Wei Wang, Weibo Wang, Gonneke Willemsen, Johannes H Smit, Eco J de Geus, Zhaoyu Yin, Brenda W J H Penninx & Dorret I Boomsma
doi:10.1038/ng.2951
Fred Wright, Patrick Sullivan and colleagues present the results of a large expression QTL study of peripheral blood using a classic twin design with follow-up replication in independent samples. Their results enable a more precise estimate of the heritability of gene expression and provide a useful resource for exploring the genetic control of transcription.
| | Letters | Top | | | | Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type pp438 - 443
Leora Witkowski, Jian Carrot-Zhang, Steffen Albrecht, Somayyeh Fahiminiya, Nancy Hamel, Eva Tomiak, David Grynspan, Emmanouil Saloustros, Javad Nadaf, Barbara Rivera, Catherine Gilpin, Ester Castellsagué, Rachel Silva-Smith, François Plourde, Mona Wu, Avi Saskin, Madeleine Arseneault, Rouzan G Karabakhtsian, Elizabeth A Reilly, Frederick R Ueland, Anna Margiolaki, Kitty Pavlakis, Sharon M Castellino, Janez Lamovec, Helen J Mackay, Lawrence M Roth, Thomas M Ulbright, Tracey A Bender, Vassilis Georgoulias, Michel Longy, Andrew Berchuck, Marc Tischkowitz, Inga Nagel, Reiner Siebert, Colin J R Stewart, Jocelyne Arseneau, W Glenn McCluggage, Blaise A Clarke, Yasser Riazalhosseini, Martin Hasselblatt, Jacek Majewski & William D Foulkes
doi:10.1038/ng.2931
William Foulkes and colleagues identify germline inactivating mutations in familial cases of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Through additional analysis of non-familial tumors, the authors find that nearly 100% of tumors carry SMARCA4 mutations and 38 of 40 lack protein expression, implicating SMARCA4 loss as the major cause of SCCOHT.
| | | | The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma pp444 - 450
Gang Wu, Alexander K Diaz, Barbara S Paugh, Sherri L Rankin, Bensheng Ju, Yongjin Li, Xiaoyan Zhu, Chunxu Qu, Xiang Chen, Junyuan Zhang, John Easton, Michael Edmonson, Xiaotu Ma, Charles Lu, Panduka Nagahawatte, Erin Hedlund, Michael Rusch, Stanley Pounds, Tong Lin, Arzu Onar-Thomas, Robert Huether, Richard Kriwacki, Matthew Parker, Pankaj Gupta, Jared Becksfort, Lei Wei, Heather L Mulder, Kristy Boggs, Bhavin Vadodaria, Donald Yergeau, Jake C Russell, Kerri Ochoa, Robert S Fulton, Lucinda L Fulton, Chris Jones, Frederick A Boop, Alberto Broniscer, Cynthia Wetmore, Amar Gajjar, Li Ding, Elaine R Mardis, Richard K Wilson, Michael R Taylor, James R Downing, David W Ellison, Jinghui Zhang & Suzanne J Baker for the St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
doi:10.1038/ng.2938
Suzanne Baker, Jinghui Zhang and colleagues report the identification of recurrent somatic mutations in the bone morphogenetic protein (BMP) receptor ACVR1 in 32% of diffuse intrinsic pontine gliomas.
See also: News and Views by Zadeh & Aldape | | | | Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations pp451 - 456
Pawel Buczkowicz, Christine Hoeman, Patricia Rakopoulos, Sanja Pajovic, Louis Letourneau, Misko Dzamba, Andrew Morrison, Peter Lewis, Eric Bouffet, Ute Bartels, Jennifer Zuccaro, Sameer Agnihotri, Scott Ryall, Mark Barszczyk, Yevgen Chornenkyy, Mathieu Bourgey, Guillaume Bourque, Alexandre Montpetit, Francisco Cordero, Pedro Castelo-Branco, Joshua Mangerel, Uri Tabori, King Ching Ho, Annie Huang, Kathryn R Taylor, Alan Mackay, Anne E Bendel, Javad Nazarian, Jason R Fangusaro, Matthias A Karajannis, David Zagzag, Nicholas K Foreman, Andrew Donson, Julia V Hegert, Amy Smith, Jennifer Chan, Lucy Lafay-Cousin, Sandra Dunn, Juliette Hukin, Chris Dunham, Katrin Scheinemann, Jean Michaud, Shayna Zelcer, David Ramsay, Jason Cain, Cameron Brennan, Mark M Souweidane, Chris Jones, C David Allis, Michael Brudno, Oren Becher & Cynthia Hawkins
doi:10.1038/ng.2936
Cynthia Hawkins, Oren Becher and colleagues report the identification of recurrent mutations in ACVR1 in 20% of diffuse intrinsic pontine gliomas.
See also: News and Views by Zadeh & Aldape | | | | Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma pp457 - 461
Kathryn R Taylor, Alan Mackay, Nathalène Truffaux, Yaron S Butterfield, Olena Morozova, Cathy Philippe, David Castel, Catherine S Grasso, Maria Vinci, Diana Carvalho, Angel M Carcaboso, Carmen de Torres, Ofelia Cruz, Jaume Mora, Natacha Entz-Werle, Wendy J Ingram, Michelle Monje, Darren Hargrave, Alex N Bullock, Stéphanie Puget, Stephen Yip, Chris Jones & Jacques Grill
doi:10.1038/ng.2925
Chris Jones, Jacques Grill and colleagues report the identification of recurrent activating mutations in ACVR1 in diffuse intrinsic pontine gliomas.
See also: News and Views by Zadeh & Aldape | | | | Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma pp462 - 466
Adam M Fontebasso, Simon Papillon-Cavanagh, Jeremy Schwartzentruber, Hamid Nikbakht, Noha Gerges, Pierre-Olivier Fiset, Denise Bechet, Damien Faury, Nicolas De Jay, Lori A Ramkissoon, Aoife Corcoran, David T W Jones, Dominik Sturm, Pascal Johann, Tadanori Tomita, Stewart Goldman, Mahmoud Nagib, Anne Bendel, Liliana Goumnerova, Daniel C Bowers, Jeffrey R Leonard, Joshua B Rubin, Tord Alden, Samuel Browd, J Russell Geyer, Sarah Leary, George Jallo, Kenneth Cohen, Nalin Gupta, Michael D Prados, Anne-Sophie Carret, Benjamin Ellezam, Louis Crevier, Almos Klekner, Laszlo Bognar, Peter Hauser, Miklos Garami, John Myseros, Zhifeng Dong, Peter M Siegel, Hayley Malkin, Azra H Ligon, Steffen Albrecht, Stefan M Pfister, Keith L Ligon, Jacek Majewski, Nada Jabado & Mark W Kieran
doi:10.1038/ng.2950
Nada Jabado and colleagues report identification of gain-of-function mutations in ACVR1, which encodes activin A receptor type I, in midline pediatric high-grade astrocytomas.
See also: News and Views by Zadeh & Aldape | | | | Genomic and molecular characterization of esophageal squamous cell carcinoma pp467 - 473
De-Chen Lin, Jia-Jie Hao, Yasunobu Nagata, Liang Xu, Li Shang, Xuan Meng, Yusuke Sato, Yusuke Okuno, Ana Maria Varela, Ling-Wen Ding, Manoj Garg, Li-Zhen Liu, Henry Yang, Dong Yin, Zhi-Zhou Shi, Yan-Yi Jiang, Wen-Yue Gu, Ting Gong, Yu Zhang, Xin Xu, Ori Kalid, Sharon Shacham, Seishi Ogawa, Ming-Rong Wang & H Phillip Koeffler
doi:10.1038/ng.2935
De-Chen Lin, Ming-Rong Wang and colleagues report exome sequencing, RNA sequencing, and copy number analyses of esophageal squamous cell carcinoma. They identified recurrent mutations in FAT1, FAT2, ZNF750, EP300 and KMT2D.
| | | | GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma pp474 - 477
Karolin H Nord, Henrik Lilljebjörn, Francesco Vezzi, Jenny Nilsson, Linda Magnusson, Johnbosco Tayebwa, Danielle de Jong, Judith V M G Bovée, Pancras C W Hogendoorn & Karoly Szuhai
doi:10.1038/ng.2927
Karolin Nord and colleagues report that GRM1 recombines with multiple genes in promoter swapping and gene fusion events in 90% of the chondromyxoid fibroma cases analyzed, resulting in GRM1 overexpression. These results implicate GRM1 rearrangement as a driver of CMF and a biomarker for this tumor type.
| | | | POT1 loss-of-function variants predispose to familial melanoma pp478 - 481
Carla Daniela Robles-Espinoza, Mark Harland, Andrew J Ramsay, Lauren G Aoude, Víctor Quesada, Zhihao Ding, Karen A Pooley, Antonia L Pritchard, Jessamy C Tiffen, Mia Petljak, Jane M Palmer, Judith Symmons, Peter Johansson, Mitchell S Stark, Michael G Gartside, Helen Snowden, Grant W Montgomery, Nicholas G Martin, Jimmy Z Liu, Jiyeon Choi, Matthew Makowski, Kevin M Brown, Alison M Dunning, Thomas M Keane, Carlos López-Otín, Nelleke A Gruis, Nicholas K Hayward, D Timothy Bishop, Julia A Newton-Bishop & David J Adams
doi:10.1038/ng.2947
David Adams, Julia Newton-Bishop, Timothy Bishop, Nicholas Hayward and colleagues identify loss-of-function variants in POT1 in several families with early onset multiple primary melanoma. They further show that these variants disrupt telomere binding by POT1 and are associated with increased telomere length.
| | | | Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma pp482 - 486
Jianxin Shi, Xiaohong R Yang, Bari Ballew, Melissa Rotunno, Donato Calista, Maria Concetta Fargnoli, Paola Ghiorzo, Brigitte Bressac-de Paillerets, Eduardo Nagore, Marie Francoise Avril, Neil E Caporaso, Mary L McMaster, Michael Cullen, Zhaoming Wang, Xijun Zhang, NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, French Familial Melanoma Study Group, William Bruno, Lorenza Pastorino, Paola Queirolo, Jose Banuls-Roca, Zaida Garcia-Casado, Amaury Vaysse, Hamida Mohamdi, Yasser Riazalhosseini, Mario Foglio, Fanélie Jouenne, Xing Hua, Paula L Hyland, Jinhu Yin, Haritha Vallabhaneni, Weihang Chai, Paola Minghetti, Cristina Pellegrini, Sarangan Ravichandran, Alexander Eggermont, Mark Lathrop, Ketty Peris, Giovanna Bianchi Scarra, Giorgio Landi, Sharon A Savage, Joshua N Sampson, Ji He, Meredith Yeager, Lynn R Goldin, Florence Demenais, Stephen J Chanock, Margaret A Tucker, Alisa M Goldstein, Yie Liu & Maria Teresa Landi
doi:10.1038/ng.2941
Maria Teresa Landi and colleagues identify a rare missense variant in POT1 shared by five melanoma-prone families from Italy and associated with increased telomere length and telomere fragility. They also identify additional familial melanoma cases with rare missense variants in POT1 and find a significant excess of rare exonic POT1 variants in melanoma cases compared to controls, implicating POT1 variants in melanoma susceptibility.
| | | | Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer pp487 - 491
Serena Nik-Zainal, David C Wedge, Ludmil B Alexandrov, Mia Petljak, Adam P Butler, Niccolo Bolli, Helen R Davies, Stian Knappskog, Sancha Martin, Elli Papaemmanuil, Manasa Ramakrishna, Adam Shlien, Ingrid Simonic, Yali Xue, Chris Tyler-Smith, Peter J Campbell & Michael R Stratton
doi:10.1038/ng.2955
Mike Stratton and colleague show that carriers of a germline copy number polymorphism involving APOBEC3A and APOBEC3B, which has been associated with increased risk of breast cancer, show more mutations characteristic of APOBEC-dependent mutational processes than cancers in non-carriers.
| | | | Low copy number of the salivary amylase gene predisposes to obesity pp492 - 497
Mario Falchi, Julia Sarah El-Sayed Moustafa, Petros Takousis, Francesco Pesce, Amélie Bonnefond, Johanna C Andersson-Assarsson, Peter H Sudmant, Rajkumar Dorajoo, Mashael Nedham Al-Shafai, Leonardo Bottolo, Erdal Ozdemir, Hon-Cheong So, Robert W Davies, Alexandre Patrice, Robert Dent, Massimo Mangino, Pirro G Hysi, Aurélie Dechaume, Marlène Huyvaert, Jane Skinner, Marie Pigeyre, Robert Caiazzo, Violeta Raverdy, Emmanuel Vaillant, Sarah Field, Beverley Balkau, Michel Marre, Sophie Visvikis-Siest, Jacques Weill, Odile Poulain-Godefroy, Peter Jacobson, Lars Sjostrom, Christopher J Hammond, Panos Deloukas, Pak Chung Sham, Ruth McPherson, Jeannette Lee, E Shyong Tai, Robert Sladek, Lena M S Carlsson, Andrew Walley, Evan E Eichler, Francois Pattou, Timothy D Spector & Philippe Froguel
doi:10.1038/ng.2939
Mario Falchi, Philippe Froguel and colleagues report association of a multi-allelic copy number variant encompassing the salivary amylase gene AMY1 with body mass index and risk of obesity.
| | | | Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31 pp498 - 502
Unnur Styrkarsdottir, Gudmar Thorleifsson, Hafdis T Helgadottir, Nils Bomer, Sarah Metrustry, S Bierma-Zeinstra, Annelieke M Strijbosch, Evangelos Evangelou, Deborah Hart, Marian Beekman, Aslaug Jonasdottir, Asgeir Sigurdsson, Finnur F Eiriksson, Margret Thorsteinsdottir, Michael L Frigge, Augustine Kong, Sigurjon A Gudjonsson, Olafur T Magnusson, Gisli Masson, The TREAT-OA Consortium, arcOGEN Consortium, Albert Hofman, Nigel K Arden, Thorvaldur Ingvarsson, Stefan Lohmander, Margreet Kloppenburg, Fernando Rivadeneira, Rob G H H Nelissen, Tim Spector, Andre Uitterlinden, P Eline Slagboom, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Ana M Valdes, Ingrid Meulenbelt, Joyce van Meurs, Helgi Jonsson & Kari Stefansson
doi:10.1038/ng.2957
Kari Stefansson and colleagues performed a genome-wide association study for severe hand osteoarthritis and found associated variants within the ALDH1A2 gene and at 1p31.
| | | | Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling pp503 - 509
Gillian I Rice, Yoandris del Toro Duany, Emma M Jenkinson, Gabriella M A Forte, Beverley H Anderson, Giada Ariaudo, Brigitte Bader-Meunier, Eileen M Baildam, Roberta Battini, Michael W Beresford, Manuela Casarano, Mondher Chouchane, Rolando Cimaz, Abigail E Collins, Nuno J V Cordeiro, Russell C Dale, Joyce E Davidson, Liesbeth De Waele, Isabelle Desguerre, Laurence Faivre, Elisa Fazzi, Bertrand Isidor, Lieven Lagae, Andrew R Latchman, Pierre Lebon, Chumei Li, John H Livingston, Charles M Lourenço, Maria Margherita Mancardi, Alice Masurel-Paulet, Iain B McInnes, Manoj P Menezes, Cyril Mignot, James O'Sullivan, Simona Orcesi, Paolo P Picco, Enrica Riva, Robert A Robinson, Diana Rodriguez, Elisabetta Salvatici, Christiaan Scott, Marta Szybowska, John L Tolmie, Adeline Vanderver, Catherine Vanhulle, Jose Pedro Vieira, Kate Webb, Robyn N Whitney, Simon G Williams, Lynne A Wolfe, Sameer M Zuberi, Sun Hur & Yanick J Crow
doi:10.1038/ng.2933
Yanick Crow, Sun Hur and colleagues show that gain-of-function mutations in IFIH1 cause a spectrum of neural and immunological phenotypes associated with enhanced interferon signaling. The mutations increase the affinity of IFIH1 for RNA, leading to immune upregulation and inflammatory disease.
See also: News and Views by Miner & Diamond | | | | De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome pp510 - 515
Ghayda M Mirzaa, David A Parry, Andrew E Fry, Kristin A Giamanco, Jeremy Schwartzentruber, Megan Vanstone, Clare V Logan, Nicola Roberts, Colin A Johnson, Shawn Singh, Stanislav S Kholmanskikh, Carissa Adams, Rebecca D Hodge, Robert F Hevner, David T Bonthron, Kees P J Braun, Laurence Faivre, Jean-Baptiste Rivière, Judith St-Onge, Karen W Gripp, Grazia M S Mancini, Ki Pang, Elizabeth Sweeney, Hilde van Esch, Nienke Verbeek, Dagmar Wieczorek, Michelle Steinraths, Jacek Majewski, FORGE Canada Consortium, Kym M Boycott, Daniela T Pilz, M Elizabeth Ross, William B Dobyns & Eamonn G Sheridan
doi:10.1038/ng.2948
Eamonn Sheridan, Elizabeth Ross and colleagues report discovery of a new megalencephaly syndrome caused by de novo missense mutations in CCND2. They show that these mutations lead to stabilization of cyclin D2, and they present evidence that cyclin D2 stabilization may be a common downstream mechanism in PI3K-AKT-associated megalencephaly syndromes.
| | | | TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function pp516 - 521
Fernando Gómez-Herreros, Janneke H M Schuurs-Hoeijmakers, Mark McCormack, Marie T Greally, Stuart Rulten, Rocío Romero-Granados, Timothy J Counihan, Elijah Chaila, Judith Conroy, Sean Ennis, Norman Delanty, Felipe Cortés-Ledesma, Arjan P M de Brouwer, Gianpiero L Cavalleri, Sherif F El-Khamisy, Bert B A de Vries & Keith W Caldecott
doi:10.1038/ng.2929
Keith Caldecott, Bert de Vries, Sherif El-Khamisy, Gianpiero Cavalleri and colleagues identify homozygous TDP2 mutations in individuals with intellectual disability, seizures and ataxia. Their follow-up studies suggest that TDP2 is required to maintain normal transcription in response to the DNA double-strand breaks induced by abortive TOP2 activity.
See also: News and Views by McKinnon | | | Top | |  | | Advertisement | | 
They're recruiting scientists just like you!
The Naturejobs Career Expo is coming to Boston, Massachusetts on May 20, 2014.
Take advantage of this free opportunity to meet employers, attend workshops and further develop your career.
Don't wait-register today! | | | | | | | | | | | | | Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here.
Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com | | | | | |
| |
|
|
No comments:
Post a Comment